Kognitiv och motorisk funktion i tidig fas av Parkinsons sjukdom.

Background: Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease. The diagnosis is based on a combination of the motor signs: tremor, bradykinesia, rigidity and postural abnormalities. Mild Cognitive Impairment (MCI) is common early in the disease and a large proportion of patients with PD develop dementia (PDD). Associations between motor symptoms and cognitive decline have been suggested but the results are inconclusive due to differences in the selection of participants and variables tested. Large population based studies with comprehensive neuropsychological investigation in newly diagnosed cases with PD followed prospectively are rare. The aim of this thesis was to improve characterization and understanding of cognition in PD, and to explore the relationship to motor impairment in the early phase of PD. Methods: All new patients with suspected idiopathic parkinsonism in the catchment area (142 ooo inhabitants) were examined during a period of five years and four months. Among other investigations, a comprehensive neuropsychological evaluation was carried out in 119 of 148 patients with PD together with 30 age matched healthy controls. Assessments were repeated after one three and five years. Results: Patients performed worse than healthy controls in a majority of neuropsychological tests. MCI at the time of diagnosis were found in 36% according to recently published MCI criteria. Thirty % were cognitively impaired using another definition. One fourth of the patients developed PDD within five years after diagnosis and 25 % of those with MCI at baseline reversed back to normal cognition. Age and MCI were significant predictors of dementia. Education was an independent predictor for severe cognitive dysfunction at diagnosis but did not predict PDD. Patients with MCI converting to PDD had worse performance on visuospatial function, semantic fluency, episodic memory, mental flexibility and conceptual thinking. There were no differences in cognitive performance between patients with predominant Postural and Gait Disturbances (PIGD) and the tremor dominant subtype at the baseline investigation and belonging to the PIGD subgroup at baseline did not predict PDD. Dementia converters declined more rapidly than non-converters in posture/gait function. Associations between bradykinesia and measures of executive functions and working memory were found, and between posture and gait disturbances and visuospatial function. Some of these associations were persistent after one year. Patients receiving the dopamine agonist pramipexole performed significantly worse on a measure of verbal fluency at the one year follow up. Conclusions: The differences in proportions of cognitively impaired in the different studies emphasize the value of joint criteria for PD-MCI. Even when using such criteria, a substantial proportion of patients revert back to normal function. The increase in motor disability in patients with PDD could have several different causes that need to be further investigated. Associated motor and cognitive dysfunctions could reflect common pathophysiological processes in partly shared networks. Both dopaminergic and non-dopaminergic motor and cognitive functions seems to be involved in PDD which suggests that pharmacological treatment in PD needs to go beyond the scope of dopaminergic deficiency in search for new therapies that would also be effective for non-motor symptoms.NYPU

On-line vs. On-site Dance for People with Parkinson’s Disease: An Evaluation Study

Background: Dance for people with Parkinson’s disease (PD) has received much attention with studies showing its benefits in terms of physical and psychological changes. As people with PD experience barriers to participate in on-site activities, home-based telehealth interventions are becoming increasingly popular. This study examined the differences between digital and on-site dance for people with PD. Methods: This evaluation study used a secondary qualitative analysis of focus group data from six participants with PD who had experience of digital and on-site dance, as well as two interviews with the dance teacher of both dance formats for people with PD. Thematic analysis was used to analyze the data. Results: Both the dancers and the dance teacher reported how the social and artistic aspects of on-site dance are not present to the same degree in digital dance. These aspects were experienced as important for acceptance of oneself and PD. Conclusions: This evaluation study demonstrates that the social and artistic aspects of dance are not experienced to the same degree within both types of dance. As these aspects were closely connected to acceptance of oneself and PD, this study encourages future efforts to focus on the social and artistic constructs within digital dance.Godkänd;2023;Nivå 0;2023-12-20 (marisr);Full text license: CC BY-NC</p

Backward relative to forward walking speed and falls in older adults with dementia

Background: Adults with dementia have a high risk of falls and fall-related injuries. A greater slowing of backward walking speed (BWS) relative to forward (FWS) has been indicated with older age, and slower BWS has been related to an increased risk of falls. Similarly, slow BWS relative to FWS has been observed in people with dementia. Research question: Is slower BWS, and slower BWS relative to FWS associated with increased risk of prospective falls in older adults with dementia? Methods: In total, 52 women and 12 men with dementia living in nursing homes, mean age 86 years, and mean Mini-Mental State Examination score of 14.2 points were included. BWS and FWS was measured over 2.4 m, and the directional difference (DD) calculated (100*((FWS-BWS)/FWS)). Falls were followed for 6 months by review of fall incident reports in electronic medical records at nursing homes and the regional healthcare provider. Results: Altogether, 95 falls occurred with mean incidence rate 3.1 falls per person-years. Of included participants, 15 (23%) fell once, and 17 (27%) fell twice or more. In negative binomial regression analyses, greater DD was associated with lower prospective incidence fall rate ratio, IRR (IRR= 0.96, p &lt; .001), while BWS was not (IRR= 0.04, p = .126). Significance: In this study of adults with dementia, slower BWS was not associated with prospective falls. However, slower BWS relative to forward (greater DD) was associated with fewer falls, and possibly a protective response. This is novel research, yet results are promising and indicate that assessing walking speed in multiple directions may inform fall risk in adults with dementia

Longitudinal changes in task-evoked brain responses in Parkinson's disease patients with and without mild cognitive impairment

Cognitive deficits are common in Parkinson's disease. Previous cross-sectional research has demonstrated a link between cognitive impairments and fronto-striatal dopaminergic dysmodulation. However, longitudinal studies that link disease progression with altered task-evoked brain activity are lacking. Therefore, our objective was to longitudinally evaluate working-memory related brain activity changes in Parkinson's disease patients with and without mild cognitive impairment (MCI). Patients were recruited within a longitudinal cohort study of incident patients with idiopathic parkinsonism. We longitudinally (at baseline examination and at 12-months follow-up) compared 28 patients with Parkinson's disease without MCI with 11 patients with Parkinson's disease and MCI. Functional MRI blood oxygen level dependent signal was measured during a verbal two-back working-memory task. Patients with MCI under-recruited bilateral medial prefrontal cortex at both time-points (main effect of group: p &lt; 0.001, uncorrected). Critically, a significant group-by-time interaction effect (p &lt; 0.001, uncorrected) was found in the right fusiform gyrus, indicating that working-memory related activity decreased for patients with Parkinson's disease and MCI between baseline and follow-up, while patients without MCI were stable across time-points. The functional connectivity between right fusiform gyrus and bilateral caudate nucleus was stronger for patients without MCI relative to patients with MCI. Our findings support the view that deficits in working-memory updating are related to persistent fronto-striatal under-recruitments in patients with early phase Parkinson's disease and MCI. The longitudinal evolution of MCI in Parkinson's disease translates into additional task-evoked posterior cortical changes

Longitudinal changes in task-evoked brain responses in Parkinson's disease patients with and without mild cognitive impairment

Cognitive deficits are common in Parkinson's disease. Previous cross-sectional research has demonstrated a link between cognitive impairments and fronto-striatal dopaminergic dysmodulation. However, longitudinal studies that link disease progression with altered task-evoked brain activity are lacking. Therefore, our objective was to longitudinally evaluate working-memory related brain activity changes in Parkinson's disease patients with and without mild cognitive impairment (MCI). Patients were recruited within a longitudinal cohort study of incident patients with idiopathic parkinsonism. We longitudinally (at baseline examination and at 12-months follow-up) compared 28 patients with Parkinson's disease without MCI with 11 patients with Parkinson's disease and MCI. Functional MRI blood oxygen level dependent signal was measured during a verbal two-back working-memory task. Patients with MCI under-recruited bilateral medial prefrontal cortex at both time-points (main effect of group: p &lt; 0.001, uncorrected). Critically, a significant group-by-time interaction effect (p &lt; 0.001, uncorrected) was found in the right fusiform gyrus, indicating that working-memory related activity decreased for patients with Parkinson's disease and MCI between baseline and follow-up, while patients without MCI were stable across time-points. The functional connectivity between right fusiform gyrus and bilateral caudate nucleus was stronger for patients without MCI relative to patients with MCI. Our findings support the view that deficits in working-memory updating are related to persistent fronto-striatal under-recruitments in patients with early phase Parkinson's disease and MCI. The longitudinal evolution of MCI in Parkinson's disease translates into additional task-evoked posterior cortical changes

Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease

Objectives: Cognitive decline is common in Parkinson's disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may be of importance. This study investigates whether genotypes associated with reduced prefrontal dopaminergic tone and/or reduced dopamine D2-receptor availability (Catechol-O-methyltransferase [COMT] Val(158)Met genotype and DRD2 (CT)-T-957 genotype) affect the development of cognitive deficits in PD. Materials and methods: One hundred and 34 patients with idiopathic PD, participating in a regional, population-based study of incident parkinsonism, underwent genotyping. After extensive baseline investigations (including imaging and biomarker analyses), the patients were followed prospectively during 6-10 years with neuropsychological evaluations, covering six cognitive domains. Cognitive decline (defined as the incidence of either Parkinson's disease mild cognitive impairment [PD-MCI] or dementia [PDD], diagnosed according to published criteria and blinded to genotype) was studied as the primary outcome. Results: Both genotypes affected cognition, as shown by Cox proportional hazards models. While the COMT(158)Val/Val genotype conferred an increased risk of mild cognitive impairment in patients with normal cognition at baseline (hazard ratio: 2.13, P=.023), the DRD2(957)T/T genotype conferred an overall increased risk of PD dementia (hazard ratio: 3.22, P&lt;.001). The poorer cognitive performance in DRD2(957)T/T carriers with PD occurred mainly in episodic memory and attention. Conclusions: The results favor the hypothesis that dopamine deficiency in PD not only relate to mild cognitive deficits in frontostriatal functions, but also to a decline in memory and attention. This could indicate that dopamine deficiency impairs a wide network of brain areas

Prediction and early biomarkers of cognitive decline in Parkinson disease and atypical parkinsonism : a population-based study

The progression of cognitive decline is heterogeneous in the three most common idiopathic parkinsonian diseases: Parkinson disease, multiple system atrophy and progressive supranuclear palsy. The causes for this heterogeneity are not fully understood, and there are no validated biomarkers that can accurately identify patients who will develop dementia and when. In this population-based, prospective study, comprehensive neuropsychological testing was performed repeatedly in new-onset, idiopathic parkinsonism. Dementia was diagnosed until 10 years and participants (N = 210) were deeply phenotyped by multimodal clinical, biochemical, genetic and brain imaging measures. At baseline, before the start of dopaminergic treatment, mild cognitive impairment was prevalent in 43.4% of the patients with Parkinson disease, 23.1% of the patients with multiple system atrophy and 77.8% of the patients with progressive supranuclear palsy. Longitudinally, all three diseases had a higher incidence of cognitive decline compared with healthy controls, but the types and severity of cognitive dysfunctions differed. In Parkinson disease, psychomotor speed and attention showed signs of improvement after dopaminergic treatment, while no such improvement was seen in other diseases. The 10-year cumulative probability of dementia was 54% in Parkinson disease and 71% in progressive supranuclear palsy, while there were no cases of dementia in multiple system atrophy. An easy-to-use, multivariable model that predicts the risk of dementia in Parkinson disease within 10 years with high accuracy (area under the curve: 0.86, P &lt; 0.001) was developed. The optimized model adds CSF biomarkers to four easily measurable clinical features at baseline (mild cognitive impairment, olfactory function, motor disease severity and age). The model demonstrates a highly variable but predictable risk of dementia in Parkinson disease, e.g. a 9% risk within 10 years in a patient with normal cognition and CSF amyloid-β42 in the highest tertile, compared with an 85% risk in a patient with mild cognitive impairment and CSF amyloid-β42 in the lowest tertile. Only small or no associations with cognitive decline were found for factors that could be easily modifiable (such as thyroid dysfunction). Risk factors for cognitive decline in multiple system atrophy and progressive supranuclear palsy included signs of systemic inflammation and eye movement abnormalities. The predictive model has high accuracy in Parkinson disease and might be used for the selection of patients into clinical trials or as an aid to improve the prevention of dementia.